dbSNP rs34838751: UNC93A:p.Ala220Val (chr6-167303952-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018974.4(UNC93A):c.659C>T(p.Ala220Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,613,430 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 174 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 175 hom. )

Consequence

UNC93A
NM_018974.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05

Publications

4 publications found

Variant links:

Genes affected

UNC93A (HGNC:12570): (unc-93 homolog A) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

UNC93A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014178157).

BP6

Variant 6-167303952-C-T is Benign according to our data. Variant chr6-167303952-C-T is described in ClinVar as Benign. ClinVar VariationId is 768119.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018974.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93A	NM_018974.4	MANE Select	c.659C>T	p.Ala220Val	missense	Exon 5 of 8	NP_061847.2
	UNC93A	NM_001143947.2		c.533C>T	p.Ala178Val	missense	Exon 4 of 7	NP_001137419.1	Q86WB7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC93A	ENST00000230256.8	TSL:1 MANE Select	c.659C>T	p.Ala220Val	missense	Exon 5 of 8	ENSP00000230256.3	Q86WB7-1
UNC93A	ENST00000366829.2	TSL:1	c.533C>T	p.Ala178Val	missense	Exon 4 of 7	ENSP00000355794.2	Q86WB7-2
UNC93A	ENST00000860147.1		c.659C>T	p.Ala220Val	missense	Exon 6 of 9	ENSP00000530206.1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3928

AN:

151420

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00791

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000629

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0178

GnomAD2 exomes

AF:

0.00674

AC:

1679

AN:

249050

AF XY:

0.00471

show subpopulations

Gnomad AFR exome

AF:

0.0925

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00274

AC:

4005

AN:

1461892

Hom.:

175

Cov.:

AF XY:

0.00236

AC XY:

1717

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0974

AC:

3261

AN:

33480

American (AMR)

AF:

0.00418

AC:

187

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000612

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000185

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000106

AC:

118

AN:

1112012

Other (OTH)

AF:

0.00644

AC:

389

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

205

410

616

821

1026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0260

AC:

3937

AN:

151538

Hom.:

174

Cov.:

AF XY:

0.0253

AC XY:

1871

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.0912

AC:

3755

AN:

41184

American (AMR)

AF:

0.00790

AC:

120

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.000629

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10510

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

67928

Other (OTH)

AF:

0.0176

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0100

Hom.:

158

Bravo

AF:

0.0308

ESP6500AA

AF:

0.0860

AC:

379

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00839

AC:

1018

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.49

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.00086

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.1

PhyloP100

2.0

PrimateAI

Benign

0.25

PROVEAN

Benign

3.0

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.044

MVP

0.18

MPC

0.24

ClinPred

0.0028

GERP RS

2.2

Varity_R

0.018

gMVP

0.22

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over